Atypical Lipomatous Tumor: Clinical, Radiological & Histology

Atypical lipomatous tumors (ALTs) are locally aggressive soft tissue neoplasms that share histological features with well-differentiated liposarcomas. While they do not metastasize, their potential for recurrence and difficulty in complete surgical removal make them clinically significant. Distinguishing ALTs from benign lipomas and more aggressive sarcomas is crucial for effective management. Diagnosis relies on clinical assessment, imaging, and histopathological analysis.

Clinical Presentation

Patients with ALTs typically present with a painless, slow-growing mass that often goes unnoticed for months or years. The absence of discomfort can delay medical evaluation, particularly for deep-seated tumors. Unlike benign lipomas, which are soft and mobile, ALTs tend to be firmer and may adhere to surrounding structures, raising suspicion for a more complex pathology. These tumors often exceed 5 cm at diagnosis, reflecting their slow yet progressive growth.

The clinical course depends on location. In the extremities, particularly the thigh, patients may experience fullness or restricted movement if the tumor encroaches on musculature. Retroperitoneal or mediastinal ALTs often remain asymptomatic until they grow large, causing compressive symptoms such as abdominal distension, early satiety, or respiratory difficulty. The absence of systemic symptoms like weight loss or fever helps differentiate ALTs from high-grade sarcomas.

Palpation findings can aid diagnosis. Superficial ALTs may resemble lipomas, but deeper lesions often have a lobulated texture with poorly defined margins. Some patients notice increasing firmness over time, suggesting fibrous changes. Unlike inflammatory masses, ALTs do not present with erythema, warmth, or tenderness.

Common Anatomical Sites

ALTs most commonly arise in deep soft tissues, particularly the thigh. The proximal lower extremity, especially the anterior and medial compartments, provides a permissive environment for tumor expansion due to abundant adipose tissue. These tumors can grow significantly before becoming noticeable, sometimes displacing neurovascular structures and causing functional impairment.

The retroperitoneum is another frequent site. Retroperitoneal ALTs often remain undiagnosed until they reach substantial sizes, exerting compressive effects on adjacent organs and causing nonspecific symptoms like early satiety, altered bowel habits, or urinary dysfunction. Displacement of major vascular structures, such as the inferior vena cava or renal vessels, can complicate surgical resection. Complete excision is particularly challenging in this location, increasing recurrence risk.

The mediastinum, though less common, presents unique challenges. Tumors in this region may remain asymptomatic for long periods before causing dyspnea, dysphagia, or chest discomfort due to mass effect. Compression of the trachea or esophagus can lead to progressive respiratory or swallowing difficulties. Imaging typically reveals a well-circumscribed, fatty mass with internal septations, distinguishing it from other mediastinal neoplasms. Surgical management is complex due to the proximity of vital cardiopulmonary structures, requiring a multidisciplinary approach.

Key Radiological Signs

Imaging is essential for distinguishing ALTs from benign and malignant soft tissue lesions. Magnetic resonance imaging (MRI) is particularly useful for evaluating tissue composition. ALTs appear as high-signal masses on T1-weighted sequences, similar to normal adipose tissue, but with thickened internal septations, nodular non-adipose components, and variable contrast enhancement. These features help differentiate ALTs from simple lipomas, which lack complex internal structures and enhancement.

Computed tomography (CT) is often used when MRI is contraindicated or for assessing deep-seated tumors. On CT, ALTs appear as well-defined, predominantly fatty masses with interspersed soft tissue elements. A hallmark feature is septal thickening exceeding 2 mm, distinguishing them from lipomas, which have thin, barely perceptible septa and no nodularity. ALTs may also exert significant mass effect, particularly in confined spaces like the retroperitoneum, where organ or vascular compression complicates surgical planning.

Fluorodeoxyglucose positron emission tomography (FDG-PET) is not routinely used but may help identify malignant transformation. ALTs generally exhibit low metabolic activity, but areas of increased FDG uptake may indicate dedifferentiation, necessitating further histopathological evaluation. This is particularly relevant in recurrent cases, where distinguishing between residual ALT and dedifferentiated liposarcoma is critical for management.

Histopathological Markers

Microscopic evaluation of ALTs reveals cellular atypia within mature adipose tissue. A defining feature is adipocytes with variable nuclear size and shape, often accompanied by scattered hyperchromatic, enlarged stromal cells. These atypical cells cluster around fibrous septa, where increased cellularity helps differentiate ALTs from benign lipomas. The presence of lipoblasts, with indented nuclei and intracytoplasmic lipid vacuoles, further supports the diagnosis, though they may be sparse.

Immunohistochemical staining is crucial for confirmation. ALTs consistently express murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4), markers overexpressed due to 12q13-15 chromosomal amplification. This genetic alteration distinguishes ALTs from lipomas, which lack MDM2 amplification. Fluorescence in situ hybridization (FISH) or quantitative polymerase chain reaction (qPCR) can detect MDM2 amplification, providing objective diagnostic support. S100 protein, a general adipocytic marker, is typically positive but lacks specificity, making MDM2 and CDK4 essential for definitive classification.

Prognostic Indicators

The prognosis of ALTs depends on tumor location, completeness of surgical excision, and risk of dedifferentiation. While ALTs do not metastasize, local recurrence is a major concern, particularly in anatomically challenging areas like the retroperitoneum and mediastinum, where achieving negative surgical margins is difficult. Recurrence rates in these locations can exceed 50%, whereas extremity ALTs, where wide excision is more feasible, have lower recurrence rates. Though recurrence does not always indicate dedifferentiation, recurrent tumors require close monitoring for histological progression.

Molecular profiling has provided additional prognostic insights, particularly regarding MDM2 amplification levels. Higher MDM2 copy numbers are associated with increased dedifferentiation risk, leading to a more aggressive clinical course. Dedifferentiated liposarcomas grow rapidly, exhibit increased cellularity, and lose adipocytic differentiation, necessitating different therapeutic approaches, including radiation or systemic therapies.

Long-term surveillance with serial imaging is recommended, especially for deep-seated tumors where subtle recurrence may go undetected. Extremity tumors are typically monitored every 6 to 12 months initially, with extended follow-up if no recurrence is detected within several years. Retroperitoneal cases may require more frequent imaging to ensure early detection of regrowth, allowing for timely intervention before significant progression.